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DOI: 10.1055/s-2007-980110
Neue Marker für das pharmakologische Targeting beim lymphogen metastasierten Harnblasenkarzinom
New Markers for Pharmacological Targeting in Bladder Cancer with Lymph Node MetastasisPublikationsverlauf
Publikationsdatum:
28. September 2007 (online)
![](https://www.thieme-connect.de/media/uro/200705/lookinside/thumbnails/10.1055-s-2007-980110-1.jpg)
Zusammenfassung
Fragestellung: VEGF-C, -D und ihr Rezeptor Flt-4 werden bei vielen Tumoren mit lymphogenen Metastasen und einer schlechten Prognose assoziiert. Wir analysierten die Expression dieser Faktoren beim lymphogen metastasierten Urothelkarzinom der Harnblase. Material und Methoden: Wir erstellten „tissue microarrays” (TMA’s) von Harnblasentumorpräparaten (HB-Array) und korrespondierenden Lymphknotenmetastasen (LK-Array) bei 73 zystektomierten und lymphadenektomierten Patienten. Nach immunhistochemischer Färbung wurden die Präparate semiquantitativ mit polyklonalen Antikörpern gegen VEGF-C, -D und Flt-4 aufgearbeitet und mit histopathologischen und klinischen Daten korreliert. Ergebnisse: Im LK-Array wurden signifikant mehr VECF-C (p = 0,007) und Flt-4 (p = 0,019) exprimiert als im HB-Array. VEGF-D korrelierte im LK-Array mit dem T-(p = 0,013) und dem N-Stadium (p = 0,030). Flt-4 korrelierte sowohl im MB-Array mit dem N-Stadium (p = 0,011) und der Femmetastasierung (p = 0,011), als auch im LK-Array mit dem T-(p = 0,004) und dem N-Stadium (p = 0,014). Ebenso hatten VEGF-D-positive Patienten beim LK-Array sowohl ein kürzeres rezidivfreies Intervall (p = 0,028), als auch ein schlechteres Gesamtüberleben (p = 0,014). Korrespondierend hatten Flt-4-positive Patienten eine kürzere Überlebenszeit (p = 0,033). Schlussfolgerung: Lymphogen metastasierte Patienten mit Urothelkarzinomen der Harnblase haben bei Überexpression von VEGF-D und Flt-4 in ihren Lymphknotenmetastasen eine schlechte Prognose. Das pharmakologische Targeting dieser Faktoren könnte zu einer Verbesserung ihres Gesamtüberlebens führen.
Abstract
Purpose: VECF-C, -D and their receptor Flt-4 are associated with lymph node metastasis and a poor prognosis in many tumour entities. We have analysed the expression of these factors in transitional cell carcinoma of the bladder with positive lymph nodes. Materials and Methods: We constructed “tissue microarrays” (TMAs) from bladder cancer specimens (BC-array) and corresponding lymph node metastases (LN-array) of 73 patients, who all underwent radical cystectomy and bilateral lymphadenectomy. After immunohistochemical staining, semiquantitative analysis was performed using polyclonal antibodies for VEGF-C, -D and Flt-4. The results were correlated with various histopathological and clinical variables. Results: VEGF-C (p = 0.007) and Flt-4 (p = 0.019) were significantly higher expressed in the LN-array compared to the BC-array. In the LN-array VEGF-D correlated with T-(p = 0.013) and N-stage (p = 0030) Flt-4 correlated with N-stage (p = 0.011) and distant metastasis (p = 0.011) in the BC-array, as well as with T- (p = 0.004) and N-stage (p = 0.014) in the LN-array. Accordingly, in the LN-array VEGF-D positive patients showed both a shorter disease-free survival (p = 0.028) and a poorer overall survival (p = 0.014). Similarly, Flt-4 positive patients had a shorter overall survival (p = 0.033). Conclusions: Patients with transitional bladder cancer and lymph node metastasis have a poorer prognosis when they overexpress VEGF-D and Flt-4 in their lymph nodes. Pharmacological targeting of these factors could improve their overall survival.
Schlüsselwörter
VEGF-C - VEGF-D - FIt-4 - Lymphangiogeness - tissue array - Karzinom der Harnblase
Key words
VEGF-C - VEGF-D - Flt-4 - lymphangiogenesis - tissue array - bladder cancer
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Dr. med. Edwin Herrmann (M.D.)
Klinik und Poliklinik für Urologie, Universitätsklinikum Münster
Albert-Schweitzer Strasse 33
48149 Münster, Germany
Telefon: (49)-251-834-7456
Fax: (49)-251-834-9646
eMail: herrmae@ukmuenster.de